Abstract
Purpose :
Age-related macular degeneration (AMD) is characterized by dysregulation of lipid homeostasis, oxidative stress, and inflammatory response, which ultimately leads to photoreceptor cell death and blindness. IGF1 holds potential as a therapeutic, as it possesses neuroprotective and anti-inflammatory effects in the brain. Despite this, its instability gives it a poor pharmacokinetic profile when delivered intravitreally. Here we describe a sustained release hydrogel that improves IGF1 activity in vivo. We hypothesize that improved IGF1 bioactivity will preserve retinal tissue in a mouse model of retinal degeneration.
Methods :
rd10 mice present with some hallmarks of AMD such as photoreceptor death and inflammation. We administered these mice with either IGF1 in saline, or IGF1 formulated in the sustain release hydrogel. A week later, mouse retinas were analyzed by immunohistochemistry for evidence of dying photoreceptors and activated microglia through TUNEL and Iba1 positive cells in the ONL, respectively. Moreover, ONL thickness was measured.
Results :
Relative to rd10 mice receiving IGF1 in saline, retinas in the hydrogel treated group showed a significant reduction in the number of TUNEL positive cells in the ONL. Microglia in the ONL was reduced in the hydrogel treated group relative to IGF1 in saline. Finally, preservation of photoreceptors was observed as determine through ONL thickness measurements.
Conclusions :
Taken together, these results suggest that IGF1 formulated in the hydrogel has improved bioactivity compared to IGF1 injected intravitreally in saline. This leads to a reduction in the inflammatory response, as well as suppression of photoreceptor cell death leading to preservation of the ONL. Longer term studies are needed to determine if the effect is sustained for multiple weeks, as well as determine if retinal function is preserved.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.